Table 2 The strengths and weaknesses of various safety strategies of CAR-T cells

Suicide switch

HSV-TK

1. powerful effect

2. extensive clinical experience

1. immunogenicity

2. clinical incompatibility

3. slow onset

4. no preventive effect for toxicity

5. premature eradication of CAR-T cells

iCasp9

1. no immunogenicity

2.clinical compatibility

2. rapid onset

1. no preventive effect for toxicity

2. premature eradication of CAR-T cells

CD20

1. no immunogenicity

2. rapid onset

1. antibody biodistribution

2. on-target toxicity from antibody

3. prodrug infusion reaction

4. no preventive effect for toxicity

5. premature eradication of CAR-T cells

EGFRt

1. no immunogenicity

2. rapid onset

3. in vivo tracking

1. antibody biodistribution

2. on-target toxicity from antibody

3. prodrug infusion reaction

4. no preventive effect for toxicity 5. premature eradication of CAR-T cells

Endogenous switch

synNotch

1. control the expression of the CARs

2. Specific recognition of tumor sites

1. uncontrolled activation of CAR-T cells 2. the choice of two antigens is difficult

iCAR

1. antigen-selectively regulate T cell responses

2. protect normal tissue from CAR-T cells

1. uncontrolled activation of CAR-T cells 2. potential “on-target, off-tumor” effect

Combinatorial Target-Antigen Recognition

1. precise killing of CAR-T cells

2. overcome antigen loss

1. uncontrolled activation of CAR-T cells

2. the choice of two antigens is difficult

3. potential “on-target, off-tumor” effect

Exogenous switch

Bispecific T Cell Engager

1. controlled activation of CAR-T cells

2. simplify manufacturing of CAR-T cells

1. The choice of small molecules needs more consideration

On-switch CAR

1. controlled activation of CAR-T cells

1. The choice of small molecules needs more consideration